1. Field of the Invention
The present invention provides peptides analogues of the native surfactant protein SP-B and their use in the preparation of formulations for the prophylaxis and/or treatment of respiratory distress syndrome (RDS) and other respiratory disorders.
2. Discussion of the Background
The human lung is composed of a large number of small air sacs, called alveoli, in which gases are exchanged between the blood and the air spaces of the lungs. In healthy individuals, this exchange is mediated by the presence of a protein-containing surfactant complex that prevents the lungs from collapsing at the end of expiration.
Lung surfactant complex is composed primarily of lipid and contains minor amounts of various proteins. An absence of adequate levels of this complex results in malfunction of the lung. This syndrome is called Respiratory Distress Syndrome (RDS) and it commonly affects preterm infants.
Said syndrome is effectively treated with modified natural surfactant preparations extracted from animal lungs.
The main constituents of these surfactant preparations are phospholipids, such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine commonly known as dipalmitoyl-phosphatidylcholine (DPPC), phosphatidylglycerol (PG) and surfactant hydrophobic proteins B and C (SP-B and SP-C) that are known to have the capacity to effect the surfactant-like activity of said preparations.
Due to the drawbacks of the surfactant preparations from animal tissues, such as the complication of the production and sterilization processes and possible induction of immune reactions, synthetic surfactants mimicking the composition of the modified natural surfactants have been developed.
Said synthetic surfactants are known as reconstituted surfactants.
However the development of clinically active reconstituted surfactants turned out to be complicated as the isolation of significant amounts of hydrophobic SP-B and SP-C proteins from natural sources is both expensive and labor intensive.
Likewise, production of these proteins by recombinant DNA techniques requires substantial effort in terms of design and achieving optimal host/vector expression systems. In addition, considerable effort is required to develop effective isolation strategies to separate and purify the expressed protein of interest from the unwanted material.
In particular the SP-B protein is characterised by high molecular weight, extreme hydrophobicity and a large number of cysteine residues which markedly complicates its commercial production via isolation from natural materials or its expression via recombinant DNA strategies.
Therefore the medical community has a need for simple, easy-to-prepare, synthetic analogues of the protein SP-B able of mimicking all the properties of the native protein.
More particularly there is a need of synthetic analogues of the protein SP-B that, when admixed with synthetic analogues of the native protein SP-C and with a lipid carrier, give rise to reconstituted surfactant preparations able of efficaciously maintaining alveolar patency at the end of expiration.